We propose the following areas of investigation: 1. To study the determinants that regulate the transcription of the tissue plasminogen activator (t-PA) gene using three experimental murine systems: a) teratocarcinoma stem cells in various stages of differentiation; b) extracts of tissues that variably express the t-PA gene; and c) growing oocytes. 2. To investigate the role of t-PA in mouse embryonic development and normal physiology by: a) examining spatial and temporal aspects of t-PA mRNA expression in the embryo and adult by in situ analysis; b) in conjunction with Aim 1, determining which regions of the t-PA promoter are instrumental in tissue-specific expression by analyzing transgenic mice containing t-PA promoter/reporter gene constructs; and C) investigating the consequences of disruption of one or both copies of the t-PA gene in mice using the techniques of homologous recombination. 3. To characterize a new type of plasminogen activator (PA) produced by a Saturnidae moth caterpillar.